Family Violence and Family Property: A Proposal for Reform

status: publishe

Molecular SPECT Imaging: An Overview

Molecular imaging has witnessed a tremendous change over the last decade. Growing interest and emphasis are placed on this specialized technology represented by developing new scanners, pharmaceutical drugs, diagnostic agents, new therapeutic regimens, and ultimately, significant improvement of patient health care. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have their signature on paving the way to molecular diagnostics and personalized medicine. The former will be the topic of the current paper where the authors address the current position of the molecular SPECT imaging among other imaging techniques, describing strengths and weaknesses, differences between SPECT and PET, and focusing on different SPECT designs and detection systems. Radiopharmaceutical compounds of clinical as well-preclinical interest have also been reviewed. Moreover, the last section covers several application, of μSPECT imaging in many areas of disease detection and diagnosis

Differences in the evolution of the ischemic penumbra in stroke-prone spontaneously hypertensive and Wistar-Kyoto rats

<p><b>Background and Purpose:</b> Stroke-prone spontaneously hypertensive rats (SHRSP) are a highly pertinent stroke model with increased sensitivity to focal ischemia compared with the normotensive reference strain (Wistar-Kyoto rats; WKY). Study aims were to investigate temporal changes in the ischemic penumbra in SHRSP compared with WKY.</p> <p><b>Methods:</b> Permanent middle cerebral artery occlusion was induced with an intraluminal filament. Diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging was performed from 1 to 6 hours after stroke, with the PWI-DWI mismatch used to define the penumbra and thresholded apparent diffusion coefficient (ADC) maps used to define ischemic damage.</p> <p><b>Results:</b> There was significantly more ischemic damage in SHRSP than in WKY from 1 to 6 hours after stroke. The perfusion deficit remained unchanged in WKY (39.9±6 mm<sup>2</sup> at 1 hour, 39.6±5.3 mm<sup>2</sup> at 6 hours) but surprisingly increased in SHRSP (43.9±9.2 mm<sup>2</sup> at 1 hour, 48.5±7.4 mm<sup>2</sup> at 6 hours; P=0.01). One hour after stroke, SHRSP had a significantly smaller penumbra (3.4±5.8 mm<sup>2</sup>) than did WKY (9.7±3.8, P=0.03). In WKY, 56% of the 1-hour penumbra area was incorporated into the ADC lesion by 6 hours, whereas in SHRSP, the small penumbra remained static owing to the temporal increase in both ADC lesion size and perfusion deficit.</p> <p><b>Conclusions:</b> First, SHRSP have significantly more ischemic damage and a smaller penumbra than do WKY within 1 hour of stroke; second, the penumbra is recruited into the ADC abnormality over time in both strains; and third, the expanding perfusion deficit in SHRSP predicts more tissue at risk of infarction. These results have important implications for management of stroke patients with preexisting hypertension and suggest ischemic damage could progress at a faster rate and over a longer time frame in the presence of hypertension.</p&gt

Imaging technologies for preclinical models of bone and joint disorders

Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy

Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra

We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2* signal change during ‘oxygen challenge’ (OC, 5 mins 100% O2). During OC, T2* increase reflects O2 binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2* acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2* signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2* and apparent diffusion coefficient (ADC) map coregistration revealed that the T2* signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2* and ADC maps coregistered with histology revealed a T2* signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra

Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging

Early diagnosis of disease and follow-up of therapy is of vital importance for appropriate patient management since it allows rapid treatment, thereby reducing mortality and improving health and quality of life with lower expenditure for health care systems. New approaches include nanomedicine-based diagnosis combined with therapy. Nanoparticles (NPs), as contrast agents for in vivo diagnosis, have the advantage of combining several imaging agents that are visible using different modalities, thereby achieving high spatial resolution, high sensitivity, high specificity, morphological, and functional information. In this work, we present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe3O4@Al(OH)3, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging. The so-prepared NPs are size-controlled, with diameters below 250 nm, completely and homogeneously coated with an Al(OH)3 phase over the magnetite cores, superparamagnetic with high saturation magnetization value (Ms = 63 emu/g-Fe3O4), and porous at the surface with a chemical affinity for fluoride ion adsorption. The suitability as MRI and PET contrast agents was tested showing high transversal relaxivity (r2) (83.6 mM−1 s −1 ) and rapid uptake of 18F-labeled fluoride ions as a PET tracer. The loading stability with 18F-fluoride was tested in longitudinal experiments using water, buffer, and cell culture media. Even though the stability of the 18F-label varied, it remained stable under all conditions. A first in vivo experiment indicates the suitability of Fe3O4@Al(OH)3 nanoparticles as a dual contrast agent for sensitive short-term (PET) and high-resolution long-term imaging (MRI).This work was supported by the European Commission under the PANA project, Call H2020-NMP2015-two-stage, Grant 686009, and partially supported by the Consellería de Educación Program for the Development of Strategic Grouping in Materials—AEMAT at the University of Santiago de Compostela under Grant No. ED431E2018/08, Xunta de Galicia, and the Flemish Agency for Innovation by Science and Technology (IWT grant agreement n◦ 140061, SBO ‘NanoCoMIT’). Furthermore, we acknowledge infrastructure funding for the preclinical PET/MRI scanner from ‘Stichting tegen Kanker’ (STK 2015-145) and from the Hercules Stichting (AKUL/13/29). Frederik Cleeren is a Postdoctoral Fellow of The Research Foundation—Flanders (FWO; 12R3119N)S

Q-VAT: Quantitative Vascular Analysis Tool

As our imaging capability increase, so does our need for appropriate image quantification tools. Quantitative Vascular Analysis Tool (Q-VAT) is an open-source software, written for Fiji (ImageJ), that perform automated analysis and quantification on large two-dimensional images of whole tissue sections. Importantly, it allows separation of the vessel measurement based on diameter, allowing the macro- and microvasculature to be quantified separately. To enable analysis of entire tissue sections on regular laboratory computers, the vascular network of large samples is analyzed in a tile-wise manner, significantly reducing labor and bypassing several limitations related to manual quantification. Double or triple-stained slides can be analyzed, with a quantification of the percentage of vessels where the staining's overlap. To demonstrate the versatility, we applied Q-VAT to obtain morphological read-outs of the vasculature network in microscopy images of whole-mount immuno-stained sections of various mouse tissues

PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide.

OBJECTIVE: The goal of this study was to measure functional and structural aspects of local neuroinflammation induced by intracerebral injection of lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [(18)F]DPA-714, magnetic resonance imaging (MRI), in vitro autoradiography and immunohistochemistry (IHC) in order to characterize a small animal model for screening of new PET tracers targeting neuroinflammation. METHODS: Rats were injected stereotactically with LPS (50 μg) in the right striatum and with saline in the left striatum. [(18)F]DPA-714 microPET, MRI, in vitro autoradiography and IHC studies were performed at different time points after LPS injection for 1 month. RESULTS: Analysis of the microPET data demonstrated high uptake of the tracer in the LPS injected site with an affected-to-non-affected side-binding potential ratio (BPright-to-left) of 3.0 at 3 days after LPS injection. This BP ratio decreased gradually over time to 0.9 at 30 days after LPS injection. In vitro autoradiography ([(18)F]DPA-714) and IHC (CD68, GFAP and TSPO) confirmed local neuroinflammation in this model. Dynamic contrast enhanced (DCE) MRI demonstrated BBB breakdown near the LPS injection site at day 1, which gradually resolved over time and was absent at 1 month after LPS injection. CONCLUSION: The LPS model is useful for first screening of newly developed tracers because of the easy design and the robust, unilateral inflammatory reaction allowing the use of the contralateral region as control. Additionally, this model can be used to test and follow up the benefits of anti-inflammatory therapies by non-invasive imaging

Characterization of a preclinical PET insert in a 7 tesla MRI scanner: beyond NEMA testing

[EN] This study evaluates the performance of the Bruker positron emission tomograph (PET) insert combined with a BioSpec 70/30 USR magnetic resonance imaging (MRI) scanner using the manufacturer acceptance protocol and the NEMA NU 4-2008 for small animal PET. The PET insert is made of 3 rings of 8 monolithic LYSO crystals (50 x 50 x 10 mm(3)) coupled to silicon photomultipliers (SiPM) arrays, conferring an axial and transaxial FOV of 15 cm and 8 cm. The MRI performance was evaluated with and without the insert for the following radiofrequency noise, magnetic field homogeneity and image quality. For the PET performance, we extended the NEMA protocol featuring system sensitivity, count rates, spatial resolution and image quality to homogeneity and accuracy for quantification using several MRI sequences (RARE, FLASH, EPI and UTE). The PET insert does not show any adverse effect on the MRI performances. The MR field homogeneity is well preserved (Diameter Spherical Volume, for 20 mm of 1.98 +/- 4.78 without and -0.96 +/- 5.16 Hz with the PET insert). The PET insert has no major effect on the radiofrequency field. The signal-to-noise ratio measurements also do not show major differences. Image ghosting is well within the manufacturer specifications (<2.5%) and no RF noise is visible. Maximum sensitivity of the PET insert is 11.0% at the center of the FOV even with simultaneous acquisition of EPI and RARE. PET MLEM resolution is 0.87 mm (FWHM) at 5 mm off-center of the FOV and 0.97 mm at 25 mm radial offset. The peaks for true/noise equivalent count rates are 410/240 and 628/486 kcps for the rat and mouse phantoms, and are reached at 30.34/22.85 and 27.94/22.58 MBq. PET image quality is minimally altered by the different MRI sequences. The Bruker PET insert shows no adverse effect on the MRI performance and demonstrated a high sensitivity, sub-millimeter resolution and good image quality even during simultaneous MRI acquisition.We acknowledge the KU Leuven core facility, Molecular Small Animal Imaging Center (MoSAIC), for their support with obtaining scientific data presented in this paper. This work was supported by Stichting tegen Kanker (2015-145, Christophe M. Deroose) and Hercules foundation (AKUL/13/029, Uwe Himmelreich) for the purchase of the PET and MRI equipment respectively. The work was supported by the following funding organizations: European Commission for the PANA project (H2020-NMP-2015-two-stage, grant 686009) and the European ERA-NET project 'CryptoView' (3rd call of the FP7 program Infect-ERA).Gsell, W.; Molinos, C.; Correcher, C.; Belderbos, S.; Wouters, J.; Junge, S.; Heidenreich, M.... (2020). Characterization of a preclinical PET insert in a 7 tesla MRI scanner: beyond NEMA testing. Physics in Medicine and Biology. 65(24):1-16. https://doi.org/10.1088/1361-6560/aba08cS1166524Balezeau, F., Eliat, P.-A., Cayamo, A. B., & Saint-Jalmes, H. (2011). Mapping of low flip angles in magnetic resonance. Physics in Medicine and Biology, 56(20), 6635-6647. doi:10.1088/0031-9155/56/20/008Benlloch, J. M., González, A. J., Pani, R., Preziosi, E., Jackson, C., Murphy, J., … Schwaiger, M. (2018). The MINDVIEW project: First results. European Psychiatry, 50, 21-27. doi:10.1016/j.eurpsy.2018.01.002Cal-Gonzalez, J., Rausch, I., Shiyam Sundar, L. K., Lassen, M. L., Muzik, O., Moser, E., … Beyer, T. (2018). Hybrid Imaging: Instrumentation and Data Processing. Frontiers in Physics, 6. doi:10.3389/fphy.2018.00047Clark, D. P., & Badea, C. T. (2014). Micro-CT of rodents: State-of-the-art and future perspectives. Physica Medica, 30(6), 619-634. doi:10.1016/j.ejmp.2014.05.011Drzezga, A., Souvatzoglou, M., Eiber, M., Beer, A. J., Fürst, S., Martinez-Möller, A., … Schwaiger, M. (2012). First Clinical Experience with Integrated Whole-Body PET/MR: Comparison to PET/CT in Patients with Oncologic Diagnoses. Journal of Nuclear Medicine, 53(6), 845-855. doi:10.2967/jnumed.111.098608Gonzalez, A. J., Aguilar, A., Conde, P., Hernandez, L., Moliner, L., Vidal, L. F., … Benlloch, J. M. (2016). A PET Design Based on SiPM and Monolithic LYSO Crystals: Performance Evaluation. IEEE Transactions on Nuclear Science, 63(5), 2471-2477. doi:10.1109/tns.2016.2522179Gonzalez, A. J., Pincay, E. J., Canizares, G., Lamprou, E., Sanchez, S., Catret, J. V., … Correcher, C. (2019). Initial Results of the MINDView PET Insert Inside the 3T mMR. IEEE Transactions on Radiation and Plasma Medical Sciences, 3(3), 343-351. doi:10.1109/trpms.2018.2866899Grant, A. M., Lee, B. J., Chang, C.-M., & Levin, C. S. (2017). Simultaneous PET/MR imaging with a radio frequency-penetrable PET insert. Medical Physics, 44(1), 112-120. doi:10.1002/mp.12031Habte, F., Ren, G., Doyle, T. C., Liu, H., Cheng, Z., & Paik, D. S. (2013). Impact of a Multiple Mice Holder on Quantitation of High-Throughput MicroPET Imaging With and Without Ct Attenuation Correction. Molecular Imaging and Biology, 15(5), 569-575. doi:10.1007/s11307-012-0602-yHammer, B. E., Christensen, N. L., & Heil, B. G. (1994). Use of a magnetic field to increase the spatial resolution of positron emission tomography. Medical Physics, 21(12), 1917-1920. doi:10.1118/1.597178Jadvar, H., & Colletti, P. M. (2014). Competitive advantage of PET/MRI. European Journal of Radiology, 83(1), 84-94. doi:10.1016/j.ejrad.2013.05.028Judenhofer, M. S., Catana, C., Swann, B. K., Siegel, S. B., Jung, W.-I., Nutt, R. E., … Pichler, B. J. (2007). PET/MR Images Acquired with a Compact MR-compatible PET Detector in a 7-T Magnet. Radiology, 244(3), 807-814. doi:10.1148/radiol.2443061756Kinahan, P. E., Townsend, D. W., Beyer, T., & Sashin, D. (1998). Attenuation correction for a combined 3D PET/CT scanner. Medical Physics, 25(10), 2046-2053. doi:10.1118/1.598392Ko, G. B., Yoon, H. S., Kim, K. Y., Lee, M. S., Yang, B. Y., Jeong, J. M., … Lee, J. S. (2016). Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging. Journal of Nuclear Medicine, 57(8), 1309-1315. doi:10.2967/jnumed.115.170019Lee, B. J., Grant, A. M., Chang, C.-M., Watkins, R. D., Glover, G. H., & Levin, C. S. (2018). MR Performance in the Presence of a Radio Frequency-Penetrable Positron Emission Tomography (PET) Insert for Simultaneous PET/MRI. IEEE Transactions on Medical Imaging, 37(9), 2060-2069. doi:10.1109/tmi.2018.2815620Loening, A. M., & Gambhir, S. S. (2003). AMIDE: A Free Software Tool for Multimodality Medical Image Analysis. Molecular Imaging, 2(3), 131-137. doi:10.1162/153535003322556877Mannheim, J. G., Schmid, A. M., Schwenck, J., Katiyar, P., Herfert, K., Pichler, B. J., & Disselhorst, J. A. (2018). PET/MRI Hybrid Systems. Seminars in Nuclear Medicine, 48(4), 332-347. doi:10.1053/j.semnuclmed.2018.02.011Maramraju, S. H., Smith, S. D., Junnarkar, S. S., Schulz, D., Stoll, S., Ravindranath, B., … Schlyer, D. J. (2011). Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI. Physics in Medicine and Biology, 56(8), 2459-2480. doi:10.1088/0031-9155/56/8/009Molinos, C., Sasser, T., Salmon, P., Gsell, W., Viertl, D., Massey, J. C., … Heidenreich, M. (2019). Low-Dose Imaging in a New Preclinical Total-Body PET/CT Scanner. Frontiers in Medicine, 6. doi:10.3389/fmed.2019.00088Nagy, K., Tóth, M., Major, P., Patay, G., Egri, G., Häggkvist, J., … Gulyás, B. (2013). Performance Evaluation of the Small-Animal nanoScan PET/MRI System. Journal of Nuclear Medicine, 54(10), 1825-1832. doi:10.2967/jnumed.112.119065Nanni, C., & Torigian, D. A. (2008). Applications of Small Animal Imaging with PET, PET/CT, and PET/MR Imaging. PET Clinics, 3(3), 243-250. doi:10.1016/j.cpet.2009.01.002Omidvari, N., Cabello, J., Topping, G., Schneider, F. R., Paul, S., Schwaiger, M., & Ziegler, S. I. (2017). PET performance evaluation of MADPET4: a small animal PET insert for a 7 T MRI scanner. Physics in Medicine & Biology, 62(22), 8671-8692. doi:10.1088/1361-6560/aa910dOmidvari, N., Topping, G., Cabello, J., Paul, S., Schwaiger, M., & Ziegler, S. I. (2018). MR-compatibility assessment of MADPET4: a study of interferences between an SiPM-based PET insert and a 7 T MRI system. Physics in Medicine & Biology, 63(9), 095002. doi:10.1088/1361-6560/aab9d1Raylman, R. R., Majewski, S., Lemieux, S. K., Velan, S. S., Kross, B., Popov, V., … Marano, G. D. (2006). Simultaneous MRI and PET imaging of a rat brain. Physics in Medicine and Biology, 51(24), 6371-6379. doi:10.1088/0031-9155/51/24/006Roncali, E., & Cherry, S. R. (2011). Application of Silicon Photomultipliers to Positron Emission Tomography. Annals of Biomedical Engineering, 39(4), 1358-1377. doi:10.1007/s10439-011-0266-9Schug, D., Lerche, C., Weissler, B., Gebhardt, P., Goldschmidt, B., Wehner, J., … Schulz, V. (2016). Initial PET performance evaluation of a preclinical insert for PET/MRI with digital SiPM technology. Physics in Medicine and Biology, 61(7), 2851-2878. doi:10.1088/0031-9155/61/7/2851Shao, Y., Cherry, S. R., Farahani, K., Meadors, K., Siegel, S., Silverman, R. W., & Marsden, P. K. (1997). Simultaneous PET and MR imaging. Physics in Medicine and Biology, 42(10), 1965-1970. doi:10.1088/0031-9155/42/10/010Steinert, H. C., & von Schulthess, G. K. (2002). Initial clinical experience using a new integrated in-line PET/CT system. The British Journal of Radiology, 75(suppl_9), S36-S38. doi:10.1259/bjr.75.suppl_9.750036Stortz, G., Thiessen, J. D., Bishop, D., Khan, M. S., Kozlowski, P., Retière, F., … Sossi, V. (2017). Performance of a PET Insert for High-Resolution Small-Animal PET/MRI at 7 Tesla. Journal of Nuclear Medicine, 59(3), 536-542. doi:10.2967/jnumed.116.187666Townsend, D. W. (2008). Combined Positron Emission Tomography–Computed Tomography: The Historical Perspective. Seminars in Ultrasound, CT and MRI, 29(4), 232-235. doi:10.1053/j.sult.2008.05.006Vandenberghe, S., & Marsden, P. K. (2015). PET-MRI: a review of challenges and solutions in the development of integrated multimodality imaging. Physics in Medicine and Biology, 60(4), R115-R154. doi:10.1088/0031-9155/60/4/r115Vaquero, J. J., & Kinahan, P. (2015). Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems. Annual Review of Biomedical Engineering, 17(1), 385-414. doi:10.1146/annurev-bioeng-071114-040723Von Schulthess, G. K., & Schlemmer, H.-P. W. (2008). A look ahead: PET/MR versus PET/CT. European Journal of Nuclear Medicine and Molecular Imaging, 36(S1), 3-9. doi:10.1007/s00259-008-0940-9Wehner, J., Weissler, B., Dueppenbecker, P. M., Gebhardt, P., Goldschmidt, B., Schug, D., … Schulz, V. (2015). MR-compatibility assessment of the first preclinical PET-MRI insert equipped with digital silicon photomultipliers. Physics in Medicine and Biology, 60(6), 2231-2255. doi:10.1088/0031-9155/60/6/2231Wehrl, H. F., Judenhofer, M. S., Thielscher, A., Martirosian, P., Schick, F., & Pichler, B. J. (2010). Assessment of MR compatibility of a PET insert developed for simultaneous multiparametric PET/MR imaging on an animal system operating at 7 T. Magnetic Resonance in Medicine, 65(1), 269-279. doi:10.1002/mrm.22591Yamamoto, S., Imaizumi, M., Kanai, Y., Tatsumi, M., Aoki, M., Sugiyama, E., … Hatazawa, J. (2010). Design and performance from an integrated PET/MRI system for small animals. Annals of Nuclear Medicine, 24(2), 89-98. doi:10.1007/s12149-009-0333-6Yamamoto, S., Watabe, T., Watabe, H., Aoki, M., Sugiyama, E., Imaizumi, M., … Hatazawa, J. (2011). Simultaneous imaging using Si-PM-based PET and MRI for development of an integrated PET/MRI system. Physics in Medicine and Biology, 57(2), N1-N13. doi:10.1088/0031-9155/57/2/n1Zaidi, H., Montandon, M.-L., & Alavi, A. (2008). The Clinical Role of Fusion Imaging Using PET, CT, and MR Imaging. PET Clinics, 3(3), 275-291. doi:10.1016/j.cpet.2009.03.00

Neuropsychopharmacology advance online publication

Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as well as for the treatment of attention-deficit hyperactivity disorder (ADHD). Although animal studies have shown neurotoxic effects of dAMPH on the dopaminergic system, little is known about such effects on the human brain. Here, we studied the dopaminergic system at multiple physiological levels in recreational dAMPH users and age, gender, and IQ-matched dAMPH-naïve healthy controls. We assessed baseline D 2/3 receptor availability, in addition to changes in dopamine (DA) release using single-photon emission computed tomography and DA functionality using pharmacological magnetic resonance imaging, following a dAMPH challenge. Also, the subjective responses to the challenge were determined. dAMPH users displayed significantly lower striatal DA D 2/3 receptor binding compared with healthy controls. In dAMPH users, we further observed a blunted DA release and DA functionality to an acute dAMPH challenge, as well as a blunted subjective response. Finally, the lower D 2/3 availability, the more pleasant the dAMPH administration was experienced by control subjects, but not by dAMPH users. Thus, in agreement with preclinical studies, we show that the recreational use of dAMPH in human subjects is associated with dopaminergic system dysfunction. These findings warrant further (longitudinal) investigations and call for caution when using this drug recreationally and for ADHD